Homer synthesis double

Certain structural indications of thromboxane A2 biosynthesis inhibition and hence potential therapeutic utility in arterial thrombosis prompted the synthesis of the pyridine prostanoid 544 (Scheme 165) (83TL3291). Brief metalation of 42 followed by DMF quench afforded aldehyde 541, which upon Homer-Emmons chain extension, reduction, and protection gave 542. Having served as a DMG, the bromo function was subjected to metal-halogen exchange, transmetalation (CuCN), and condensation with an iodo allene to furnish the 3,4-disubstituted pyridine 543. The latter was transformed into two derivatives 544 (with and without double bond), which were shown to be effective inhibitors of thromboxane A2. 

In many cases, the second side chain of the cyclopentane ring of prostaglandins possesses a double bond with ( )-geometry at C-13. The introduction of this side chain is usually achieved by olefination with phosphonate anions according to the Homer technique. However, because of the vicinal oxygen function at C-15 it is also recommended to introduce the side chain via ( )-stereoselective Wittig synthesis... 

Pommer et al.146) reported a synthesis of a stereoisomer mixture of JH1 using a Homer-Wadsworth-Emmons olefmation for introducing the double bond at C-2 of 184146). Three Wittig olefinations were applied in the condensation of C4 + C6 + + C5 + C2 synthons 147). The isomers obtained were separated by distillation (Scheme 35). 

For the synthesis of disubstituted alkenes by the Homer reaction, diere are general guidelines that can be followed to maximize selectivity, as shown in structure (246). It is best to have the larger of the two substituents of the double bond to be formed derived ffom the carbonyl moiety. This is particularly important if the substituent is anion-stabilizing since this will erode the selectivity at the elimination. These rules can be followed, regardless as to the stereochemistry of the alkene desired. 

Wittig-Horaer reaction to give vitamin D2. The unique feature of this synthesis is the synthesis and preservation of the Z-geometry of C-5,6 double bond while the final step of the Wittig-Homer reaction allows the selective formation of J -geometry for the C-7,8 olefin. 

The results of the olefination reactions obtained with the Reformatsky approach are similar to those of the Wittig-Homer and the Homer-Wadsworth-Emmons methodologies. But in contrast to these, the position of the newly formed double bond in the Reformatsky approach is not always certain, as exemplified in the synthesis of the kappa opiate agonist [ C]PD-17,30212461. where a mixture of double bond isomers 242 and 243 was obtained. In this case, fortunately, the lack of selectivity was unimportant because both were... 

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